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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
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Updated: Sep 20, 2025

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
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A Multitrait Locus Regulates Sarbecovirus Pathogenesis.

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    Genetic variation impacts infectious disease susceptibility. Mouse models reveal key genes, CCR9 and CXCR6, influencing SARS-CoV and SARS-CoV-2 severity, offering insights into human disease.

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    Area of Science:

    • Genetics
    • Immunology
    • Virology

    Background:

    • Genetic variation significantly influences host susceptibility to infectious diseases, including viral infections.
    • Traditional human Genome-wide Association Studies (GWAS) face challenges in dissecting the genetic underpinnings of infectious disease outcomes.
    • Mouse models offer experimental control and precision for studying host genetics in infection.

    Approach:

    • A genetic mapping cross was performed between two distinct Collaborative Cross mouse strains to analyze severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes.
    • Quantitative trait loci (QTL) analysis was employed to identify genetic loci associated with differential disease responses.
    • Candidate genes within identified loci were further investigated for their role in regulating viral disease severity.

    Key Points:

    • Several loci were identified that control differential disease outcomes in response to SARS-CoV infection.
    • A conserved synteny locus on mouse Chromosome 9, homologous to a human GWAS locus for severe SARS-CoV-2 disease, was identified.
    • The candidate genes CCR9 and CXCR6 were confirmed to play a crucial role in regulating disease severity across SARS-CoV, SARS-CoV-2, and a bat sarbecovirus.

    Conclusions:

    • Experimental mouse crosses provide a powerful template for identifying and characterizing multitrait loci that regulate pathogenic infectious outcomes.
    • The identified genes CCR9 and CXCR6 are critical regulators of sarbecovirus infection severity.
    • This research bridges findings from mouse models to human genetic studies of viral diseases.